(i) Field of the Invention
The present invention is a method for preparing .alpha.-(4-isobutylphenyl)propionic acid or its precursor, i.e., an alkyl .alpha.-(4-isobutylphenyl)propionate, .alpha.-(4-isobutylphenyl)propionaldehyde or 2-(4-isobutylphenyl)propanol economically and in a high purity.
More specifically, the present invention relates to an ecomonical method for preparing .alpha.-(4-isobutylphenyl)propionic acid or its precursor which comprises a dehydrogenation step of dehydrogenating p-isobutylethylbenzene in a gaseous phase in the presence of a dehydrogenating metal catalyst to form olefins including p-isobutylstyrene and the like as by-products; a carbonylation step of reacting the formed p-isobutylstyrene with carbon monoxide and water or an alcohol in the presence of a transition metal complex carbonylating catalyst to form .alpha.-(4-isobutylphenyl)propionic acid or its precursor; and a hydrogenation step of hydrogenating the formed olefin by-products to convert the same into p-isobutylethylbenzene and hydrogenating the other by-products formed in the carbonylation step to form .alpha.-(4-isobutylphenyl)propionic acid or its precursor.
This .alpha.-(4-isobutylphenyl)propionic acid is a useful medicine (trade name Ibuprophen) having alleviation effects of fever and pain and antiphlogistic effect, as described in British Patent No. 971700 and French Patent No. 1549758.
On the other hand, it is known that the alkyl .alpha.-(4-isobutylphenyl)propionate can be easily converted into .alpha.-(4-isobutylphenyl)propionic acid by hydrolysis with an acid or an alkali in a known manner. Similarly, it is also known that .alpha.-(4-isobutylphenyl)propionaldehyde and .alpha.-(4-isobutylphenyl)propanol can be easily converted into .alpha.-(4- ) isobutylphenyl)propionic acid by oxidation in a known manner. Therefore, these compounds can all be considered to be the precursors of .alpha.-(4-isobutylphenyl)propionic acid.
(ii) Description of the Prior Art
Heretofore, .alpha.-(4-isobutylphenyl)propionic acid and its precursor have been synthesized from an extremely great number of compounds as starting materials by various methods.
However, in order to synthesize .alpha.-(4-isobutylphenyl)propionic acid and its precursor at a low cost and in a high purity, the following requirements are needful:
(a) Starting materials should be simple compounds.
(b) In a reaction to be utilized, an intermediate in each step should also be as simple and stable as possible.
(c) In place of expensive reagents, inexpensive reagents or catalysts should be employed.
(d) It is necessary that by-products can be effectively utilized.
(e) The number of steps for the synthesis should be as few as possible.
(f) Since an isobutyl group is liable to bring about isomerization, it is necessary to use a reaction in which the isomerization and other undesirable phenomenons are inhibited as much as possible.
For example, in Japanese Patent Laid-open Publication No. 52-65243 and U.S. Pat. No. 3959364 which suggest synthetic methods of .alpha.-(4-isobutylphenyl)propionic acid or its alkyl esters, complicate and expensive compounds or Grignard reagents which are unstable and difficult to handle are utilized as starting materials themselves. Therefore, these suggested methods are not always considered to be economical from an industrial viewpoint.
Additionally, in all of Japanese Patent Laid-open Publication No. 50-4040 which disclose methods for the preparation of .alpha.-(4-isobutylphenyl)propionic acid, isobutylbenzene is used as the starting material, but aluminum chloride is used as a catalyst, and thus, an isobutyl group tends to isomerize. In addition, expensive reagents are used.
In methods described in French Patent No. 1549758, British Patent Nos. 1160725 and 1549140, U.S. Pat. Nos. 3965161 and 4143229, Japanese Patent Laid-open Publication Nos. 52-57338, 52-97930, 53-18535 and 56-154428, p-isobutylacetophenone is used as the starting material.
However, p-isobutylacetophenone is not considered to be an inexpensive compound for the undermentioned reason. The most economical synthesis of p-isobutylacetophenone is to use isobutylbenzene as the starting material, but it is not preferable from an economical viewpoint to convert isobutylbenzene into p-isobutylacetophenone. That is, for the sake of the conversion into p-isobutylacetophenone, it is indispensable to make use of acetyl chloride which is an expensive and unstable material, and in addition, anhydrous aluminum chloride which is very sensitive to water must be used as a reaction catalyst at least in an amount equimolar with acetyl chloride, i.e., in a large amount. For example, even if this conversion reaction proceeds stoichiometrically in a yield of 100%, anhydrous aluminum chloride as much as 700 kg must be used to manufacture 1 ton of p-isobutylacetophenone. Moreover, after the end of the reaction, 410 kg of aluminum hydroxide and 750 kg of a chlorine ion result from the inactivation of anhydrous aluminum chloride, and thus it is additionally necessary to treat 1,160 kg of wastes, the amount of which is much greater than that of the manufactured p-isobutylacetophenone, so as to make them harmless. For this reason, needless to say, p-isobutylacetophenone itself as the starting material is expensive. Furthermore, the conversion of p-isobutylacetophenone into .alpha.-(4-isobutylphenyl)propionic acid or its alkyl esters proceeds via intricate intermediates, and it is fair to say that the known method is not always economical from an industrial viewpoint.
Japanese Patent Laid-open Publication Nos. 52-97930 and 59-10545 and US Patent No. 4329507 suggest methods for preparing .alpha.-(4-isobutylphenyl)propionic acid from p-isobutylstyrene through a hydroformylation reaction or a Reppe reaction. These methods using p-isobutylstyrene are economically excellent as techniques for preparing .alpha.-(4-isobutylphenyl)propionic acid, because p-isobutylstyrene which is the starting material is simple and stable, and because the hydroformylation reaction and the Reppe reaction do not require expensive reagents. However, in these conventional manufacturing methods of p-isobutylstyrene, a complex reaction route is taken or expensive reagents are employed, so that the above-mentioned advantages are lost.
U.S. Pat. No. 4694100 discloses a method which comprises subjecting isobutylbenzene and acetaldehyde to condensation reaction in the presence of a sulfuric acid catalyst to form 1,1-bis(p-isobutylphenyl)ethane, catalystically decomposing the latter to p-isobutylstyrene by the use of an acid catalyst, reacting the resultant compound with carbon monoxide and water or with carbon monoxide and an alcohol in the present of a carbonylation complex catalyst in order to obtain .alpha.-(4-isobutylphenyl)propionic acid or its alkyl ester. However, since the above-mentioned method employs sulfuric acid, the sulfonation reaction of isobutylbenzene itself which is the valuable raw material for the manufacture of 1,1-bis(p-isobutylphenyl)ethane cannot be avoided, so that a part of isobutylbenzene is lost as a sulfonated compound, which means that the method is economically unpreferable. In addition, since this condensation reaction is a dehydration reaction, sulfuric acid which is used as the catalyst is diluted with the resulting water, and thus in order to reuse the catalyst, the diluted sulfuric acid must be treated by, for example, high-temperature distillation, in which devices are inconveniently liable to corrode. Additionally, a great deal of the sulfonated compound is dissolved in a sulfonic acid phase, and therefore the catalyst concentration cannot be easily recovered by the simple distillation. In consequence, the resultant water must be removed through chemical reaction by the use of anhydrous sulfuric acid or fuming sulfuric acid, with the result that the cost of the catalyst increases.
As discussed above, the conventional techniques regarding the manufacture of .alpha.-(4-isobutylphenyl)propionaldehyde or its alkyl ester are not considered yet to be economical.
As already described, p-isobutylstyrene is a useful intermediate in manufacturing .alpha.-(4-isobutylphenyl)propionic acid, and if this p-isobutylstyrene is utilized, .alpha.-(4-isobutylphenyl)propionic acid can be prepared inexpensively and easily. Accordingly, a novel method for this p-isobutylstyrene is desired.
By way of one technique of manufacturing p-isobutylstyrene at a low cost, the dehydrogenation of p-isobutylethylbenzene can be considered.
However, in the product by subjecting p-isobutylethylbenzene to the dehydrogenation reaction, olefin by-products are inevitably present to some extent together with p-isobutylstyrene. In addition, inventors of the present application have found the following fact through experiments: Some compounds of the above-mentioned olefin by-products are sensitive to hydroformylation, hydrocarboxylation or hydroesterification, and therefore they trigger troubles in the carbonylation of p-isobutylstyrene. In view of the object of the present invention that a medicine or its precursor is prepared, necessary means must be taken so as to eliminate the unpreferable functions of these olefin by-products in the carbonylation step.